The cytochromes P-450 are central to the activation and detoxification of xenobiotics, to drug metabolism and to the activation and detoxification of carcinogens. Whether a potentially carcinogenic molecule is metabolized to an active carcinogen or to an excretable form may depend on the activity and substrate specificity of the forms of the P-450s which predominate in the target tissue. As a result of this, susceptibility to cancer induction may well depend on the regulation of expression of the genes for specific cytochrome P-450. We are using recombinant DNA techniques and other state-of-the-art molecular biological methodologies to study the structure and the regulation of the genes for the P-450s. We have constructed cDNA clones complementary to methylcholantrene induced P-450 mRNA, and are constructing equivalent cDNA clone complimentary to phenobarbital-induced P-450 mRNA. These cDNA clones are being used to clone the complete, native genes for these P-450s. We will use these recombinant molecules to study the structure of the P-450 genes and the regulation of expression of these genes.